Renal adenocarcinoma is a common malignancy of adults which is poorly responsive to conventional chemotherapy. Glycosphingolipids are ubiquitous and complex glycocongugates which have been implicated in the growth and differentiation of many types of malignancies. The recent development and application of specific inhibitors of glycolipid metabolism, as well as homologously related compounds, by the investigators provides a novel and potentially useful approach to the treatment of this cancer possibly through inhibition of metastasis. We propose to study the functional roles played by glycosphingolipids in the growth of renal adenocarcinoma and evaluate the potential treatment of renal cell carcinoma by the inhibition of glycosphingolipid synthesis. The following questions are to be addressed in this proposal. What are the effects of inhibition of glucosylceramide synthase by 1- phenyl-2-decanoylamino-3-morpholino-1-propanol, beta-glucosidase by conduritol B epoxide, and of 3-ketodihydrosphingosine synthase by cycloserine on the growth of cultured renal adenocarcinoma cells? What is the role of protein kinase C activity in mitogen stimulated renal cell carcinoma proliferation? Is the inhibition of growth resulting from glucosylceramide synthase inhibition mediated by changes in protein kinase C? Is the inhibition of growth mediated by changes in cellular adherence to extracellular matrix proteins? What are the growth characteristics of renal adenocarcinoma cells implanted in mice which are then treated with glucosylceramide synthase inhibitors?